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Antiretroviral drugs are used to combat HIV Scientists are testing a vaccine designed to give HIV patients a prolonged break from their regular medication without side effects.

The Aids 2008 conference in Mexico City was told 345 patients in 21 centres in the US and Europe will take part in the largest-ever trial of its kind.

The vaccine has been developed by a biotechnology company based in Norway, Bionor Immuno.

Results from the trial are due by the end of 2009.

A break from standard HIV therapy would potentially alleviate the adverse side effects associated with the drugs, and help delay the emergence of drug-resistant viruses, as well as providing substantial savings for health care services.

Dr Barry Peters, of Kings College London, is leading the research in the UK.

He said: "A successful immunotherapeutic HIV vaccine would give patients and doctors enormous advantages over current treatments, both in developed and developing countries.

"Even if this vaccine is not the final answer, it could help the march towards a successful immunotherapeutic HIV vaccine."

The vaccine, which works by stimulating an immune system response, has already been tested in two small trials on 11 and 38 HIV patients with promising results.

The majority of patients were able to refrain from taking their usual antiretroviral therapy (ART) for an average period of 31 months.

During this time their level of key infection-fighting CD4+ cells remained high above the level they had before they started taking ART.

At a follow up 44 months after treatment interruption, 34% of the patients were still not back on ART.

Some patients were still off ART five years after the trial was completed.

ART cannot usually cannot be interrupted for more than three to four months without side effects.

If you'd like to check out a cool PDF presentation on the vaccine, Google "hiv Bionor Immuno" and look for the PDF file which should be about 9 entries down on the first page.

so so so so so exciting!!! very very good news. amazingi just posted on this too wowi feel hopeful, this is wonderfuleveryone on meds -- norway finds something great31 to 44 months is very very long time to be free of meds!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Bionor Immuno Advances HIV Peptide-Based Therapeutic Immunization Program with Start of a Phase IIb Trial in U.S. and EuropeA new innovative therapeutic immunization designed to help existing HIV and AIDS patients enjoy prolonged drug - and side effect - free periods was announced today at the AIDS 2008 conference in Mexico City

Last update: 10:01 p.m. EDT Aug. 4, 2008MEXICO CITY, Aug 04, 2008 (BUSINESS WIRE) -- Bionor Immuno today announced that it has advanced its efforts to develop the first HIV therapeutic immunization with the dosing of patients in a global Phase 2b clinical trial of the company's lead candidate (Vacc-4x). This randomized, double-blind, placebo-controlled trial is being conducted in HIV infected patients with the potential to offer an important drug free break in their current antiretroviral therapy. The company anticipates that trial results will be available by year end 2009."The commencement of this global Phase 2b study represents an important milestone in the clinical development of our Vacc-4x therapeutic peptide candidate," said Birger S0rensen, President and CEO of Bionor Immuno. "In previous clinical studies, this peptide therapeutic candidate has demonstrated promising results in T-cell stimulation of the immune system in HIV patients. Bionor is excited to provide a potential significant step forward for treatment alternatives in the management of HIV disease."Earlier observations of HIV patients showed that sustained immune responses to the protein p24 in the HIV virus were associated with delayed disease progression. Building on this observation, Vacc-4x is comprised of 4 modified synthetic peptides, each of which correspond to a conserved domain of the p24 protein. The modified peptides in Vacc-4x are designed to amplify and extend immunity to this protein, which could allow for extended drug free periods and may delay disease progression.Dr. Barry Peters, Head of the Academic Unit of HIV & STDs at the Guys & St Thomas' site of Kings College London, is leading the research in the UK and has 20 years of clinical experience of managing people with HIV infection. He says: "A successful immunotherapeutic HIV vaccine would give patients and doctors enormous advantages over current treatments, both in developed and developing countries. Even if this vaccine is not the final answer, it could help the march towards a successful immunotherapeutic HIV vaccine."Dr. Richard Pollard, Head of the Infectious Diseases Division at The University of California, Davis Medical School, Sacramento, California, says "this is the largest current therapeutic vaccine trial in the world involving 345 patients. This trial will establish a solid foundation for HIV immune therapies if we can maintain immunogenicity during drug free periods.About Vacc-4x Peptide Therapeutic CandidateVacc-4x has been tested in two clinical trials exposing the vaccine to 11 and 38 HIV patients, respectively. In both studies the vaccine was found to be safe and well tolerated. In the phase IIa study comprising 38 patients, the primary objective was to measure immune responses to Vacc-4x. Subjects were initially maintained stable on ART (Antiretroviral Therapy) while treated over a period of 26 weeks with a series of Vacc-4x immunizations at a low dose (LD) or high dose (HD). This immunization phase included also an ART-free window during which endogenous antigen stimulation was allowed.-- The majority of subjects experienced a pronounced therapeutic effect allowing them to remain off ART following completion of the study (Week 52). While being off ART the patients CD4+ cell counts remained high above the level they had before they had ART commenced by their treating physician.-- Due to this pronounced clinical response permission was granted to follow the subjects until they resumed ART. The median treatment interruption achieved for all subjects in the Vacc-4x Phase IIa clinical study was 31 months. The duration of treatment interruption was linked to immune responsiveness to the peptides.-- At a follow up 44 months after treatment interruption, 34% of the patients were still not back on ART treatment. For the full appreciation of these unique data it should be noted that previous experience has shown that ART usually cannot be interrupted for more than 3-4 months.About Bionor ImmunoBionor Immuno AS is an innovative biotech company developing synthetic peptide vaccines that stimulate cell mediated immunity. Previous efforts made to utilize T-cell stimulation for a vaccine have been notoriously unsuccessful and this is also the reason why such vaccines are not on the market today. Bionor Immuno carefully designs synthetic (modified) peptides with improved efficacy and safety profiles. Among the diseases targeted are chronic infections caused by HIV, HCV (Hepatitis C), HPV (Human Papilloma Virus) and Influenza. Bionor Immuno's platform technology is universally applicable makes it possible to extend the range of projects to include also vaccines targeting common cancer diseases. www.bionorimmuno.com.

Peptides are designed such that upon uptake by dendritic cells and following antigen processing,epitopes are preserved and reach the cell surface either bound to HLA class I and/or class II molecules.This in turn will lead to the stimulation of CD4+ and CD8+ T-cells respectively. (Sommerfelt et al, 2004)

In the course of a natural infection, immune responses to the pathogen can be poorly effective ateradicating the infection. Bionor Immuno identifies regions on viral proteins that are conservedacross multiple strains. These regions are used as a basis for developing peptides (protein fragments)for future candidate therapeutic or preventative vaccines. The peptides are modified by amino acidsubstitution to enhance their potential to induce an effective immune response. Peptide selection andmodification are based on an in house developed peptide design technology.

The peptides are designed to be taken up by dendritic cells of the skin following intradermalinjection. Granulocyt macrophage colony stimulating factor (GM-CSF) is also injected intradermallyat the same site as a local adjuvant because of its known effects on dendritic cell maturationand migration. Dendritic cells are targeted because they are the most potent antigen presentingcells. When the dendritic cells have taken up the peptides they transport them to the regionallymph nodes. Here they stimulate T-cells to recognise and attack specific viral proteins.Synthetic peptides are particularly useful and safe immunogens:

• They do not carry any genetic material• They are not replication competent• Have few transient minor side effects (e.g. transient tiredness and flu –like symptoms).• Allow for unlimited boosting• Allow for cost-effective large-scale production• Are safe to administer to people of all ages

The peptides are designed to be taken up by dendritic cells of the skin following intradermalinjection. Granulocyt macrophage colony stimulating factor (GM-CSF) is also injectedintradermally at the same site as å local adjuvant because of its known efects on dendritic cellmaturation and migration. Dendritic cells are targeted because they are the most potent antigenpresenting cells. When the dendritic cells have taken up the peptides they transport them to theregional lymph nodes. Here they stimulate T-cells to recognise and attack specific viral proteins.

NEWS 2008Bionor Immuno receives a grant from The Research Councilof Norway’s user-driven research (BIA) programme <<Back

The Norwegian Research Council has awarded Bionor Immuno a three year grant towardsthe development of Peptide-induced humoral responses to the carboxyterminal C5 regionof gp120 as a novel HIV-1 immunotherapeutic intervention. The work will be carried outin collaboration with the Norwegian Institute of Public Health in Oslo,Norway and St. Georges University of London, United Kingdom

You should have read our posting guidelines found in the Welcome Thread before you started becoming abusive to members. You've already had your PM privledges removed for sending abusive PMs, and now you're being given a seven day time out for being abusive in the forums.

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

At a follow up 44 months after treatment interruption, 34% of the patients were still not back on ART

This is politely speaking, a bloody poor show. It's half as effective as current combo on an intent-to-treat basis and near on 1/3rd as effective on an on-treatment basis.

Given the data from the SMART study on what happens to your body in terms of immune activation when you stop combo, I have serious concerns about the 1/3rd - 2/3rd of people in this study who effectively took a treatment break and have therefore allowed unchecked, or partially checked, HIV replication to damage their body further.

The immunological science for HIV control by the body is extremely difficult and incomplete. Promising, worth following up, but once again more unfounded optimism and talking up from the press and PR people without much questioning of the science and scientists eg on safety.

For example, ACTG 5170 prospectively followed 167 patients for 96 weeks who stopped treatment, after having previously been stable on >/=2 drug combinations for at least 6 months.The median time off treatment here was 22 months, with a very wide range. As with the Vacc-4x studies, the participants in all the studies mentioned in the report noted above had generally high (400+) CD4 counts and had been stable on combo for 6 months.

Last update: 5:12 p.m. EDT Aug. 5, 2008MONTREAL and DURHAM, N.C., Aug 05, 2008 (BUSINESS WIRE) -- Argos Therapeutics and Universite de Montreal today announced the presentation of new information on Argos' process for developing dendritic cell-based immunotherapies for HIV. Results from the study demonstrate that loading monocyte-derived dendritic cells with combinations of HIV antigen RNA stimulates the expansion of HIV-specific T cells, which attack and kill HIV-infected cells. Argos' immunotherapies are generated by the Company's Arcelis(TM) technology, which is a platform for creating autologous, RNA-loaded dendritic cell-based therapies perfectly matched to each patient's unique virus. These data were presented in an oral poster discussion August 5, 2008 at the XVII International AIDS Conference in Mexico City."A key step in the durable control of HIV infection requires enhancing the development of memory immune responses and the stimulation of potent cytotoxic T cells through therapeutic vaccination," said Charles Nicolette, Ph.D., Chief Scientific Officer of Argos. "Working with our colleagues at the Universite de Montreal, we have shown that Argos' approach of transfecting dendritic cells with autologous, HIV-specific antigens effectively activates dendritic cells and enhances the HIV-specific T cell response. We believe that these results support our methods of developing potent immunotherapies that help patients' immune systems more effectively fight HIV infection."The inability of the immune system to effectively mount a response against HIV may be caused by a defect in the maturation of T cell memory. To explore this hypothesis, researchers from Dr. Rafick-Pierre Sekaly's laboratory at the Universite de Montreal and Argos tested whether modified dendritic cells, http://www.marketwatch.com/news/story/argos-therapeutics-universite-de-montreal/story.aspx?guid={A6F60E69-01D9-4447-9BF9-EBBF81233AA4}&dist=hppr

yes at least they are trying to create a vaccine therapy without side effectsso my hope is that it would be give a new vaccine every month or every 3 monthsalong with the dentric cell vaccine which montreal is testingthere is great stuff, it will take many months for all the AUTHORITIES to review and for additional trialsbut seems to me therapeutic vaccines are on the horizonthey could be used in combo toodendric, b cell, t cell, cd4 cell are all different vaccinesso many steps many hopesi think when the dust settles from mexico there will be some good newsfor all of usregarding those who have veen saved saved by haart, i was saying those who haart is working have been saved by haart and hopefully therapudic vaccines can help others see my posts in activism i always post to help and save and work toward those who are failing regimentsthat is most important

Bionor's 31 months would possibly allow sufficient time for other(including Bionor's) therapeutic vaccines to emerge. Bionor is also developing another therapeutic hiv vaccine called VACC5q, which looks to be a successor to the VACC4x. Perhaps, the latter will be available within the 31 month time frame. "Even if this vaccine is not the final answer, it could help the march towards a successful immunotherapeutic HIV vaccine.?"

I am gonna give my view on (1) the timeline for development of immune based treatments (2) what's right, wrong and the whys and wherefores of the reports and science -- two different things -- of the Vacc 4X etc stuff (3) a general future view of treatment, and what activists need to ask to get the best out of research

(1) 5-10 years, probably towards the 10 end, this is a pretty standard range for development of a new therapeutic agent. Immune based treatments are difficult, which is why £££ earning pharma companies concentrate on pills

(2) What's right,

..it is extremely interesting, and promising, and some very good brains are involved.

Good enough for a phase III randomised placebo controlled trial to be mounted in the US and Europe starting soon (there are of course some pointed ethical and clinical issues here about effectively giving a treatment break to people who need it bearing in mind the data from the SMART study et al about the effects of resurgent viraemia, but hey...informed consent right?)

I look forward to the interim and final results. They won't be as good as the phase II, cos they usually aren't, but they will be good I hope...

.. the reporting, like the gung-ho, no checking we read the press release stuff. Is there still such a thing as fact checking? The widely circulated reports contain at least one inconsistency (can you spot it?) and many unsupported value judgements. The studies mentioned in the press release are at least 6 months old and have been published/discussed at conferences elsewhere (this is a World AIDS Conference thing, nearly nothing is genuinely new). No reporter has questioned the safety or potential different efficacy of a this vaccine compared to standard of care, in particular the bad effect of low level viraemia and what this means (cos its bad). For all its side effects, at least combo stops HIV dead in its tracks.

..the detail, like 26 weeks injections on and off, the HLA-related componet of effectiveness (ie worked better for some people depending on the make up of their immue system, and not at all for some), the comparison with people on a break but no vaccine and whether there is a meaningful difference, the unknown long-term side effects etc.

I want to know:

- what were the viral loads of people off treatment on the vaccine? did they get ill (for any reason) more often than people on combo?- what was the virus doing to their bodies during the 2-3 year break?- how many people, as a proportion, derived no immune-boosting benefit?- did the other immune modulating factors given with the vaccine cause problems, eg injection site reactions, flue like symptoms etc? did the patients find the whole treatment experience fitted with their real lives?- how many of the study participants were emotionally committed because they believed combo was A BAD THING?

etc

(3) Immune therapies hold a great deal of promise, and are the next big STEP, but it's a big one, and it's a moot point whether people who's immune systems are damaged by HIV will benefit, or whether the real shot at improved health will be confined to intervention early in the course of infection. They will not be for everyone, because immunity is so closely bound up with HLA/genetics/serotypes. They will be fiddly.

Activists need to ask the type of questions noted above, and make companies produce sufficient data/design in data capture to make answering these questions easy. the question of safety and efficacy, esp for pregnant women and in hepatitis coinfection, need pushing hard. Activists also need to learn the difference between a press release and science.

Hope is important, I am hopeful, but as someone has already said, I am a hard man to impress. I have made a GSK rep sweat over their data on abacavir and heart disease, and then said thank you for a relatively good drug. This is how it needs to be. This is what it means to be a treatment activist: to have hope, to question, to know the difference between PR and science, to demand bloody good results, to say thank you when they are delivered.

Here endeth the lesson, I taketh off my dog collar now and slippeth into my shorts and harness